Pluripotent and multipotent stem cells have the potential to revolutionize various therapeutic applications, especially in the fields of regenerative medicine and pharmaceutical development. One of the obstacles for stem cell-based therapy is the requirement of large numbers of cells, which can be met by expanding stem cells without differentiation, culturing in a large scale. A number of technical hurdles remain for expansion of such cells using the currently available substrates for cell-culture.
Bioreactors have long been practiced as the preferred scale-up method for cell culture. The use of microcarriers for culturing adherent cells is common in industrial bioprocessing. Typical bioreactor vessels employ some means of agitation, such as internal impellers, rocking or shaking mechanisms to suspend the cells and allow mass transfer of nutrients, oxygen and metabolic waste products. The agitation can subject cells to high degrees of flow-induced stress that can damage cells, especially sensitive ones such as stem cells. Carriers that can protect stem cells from agitation-induced damage and provide better stem cell recovery have recently been developed. In some cases, macrocarriers are used to facilitate easy separation of the carriers from the cells during passaging, and preventing the formation of cell-carrier aggregates.
In a bioreactor, growing adherent cells on macrocarriers (mm-size) may be subject to an issue of carrier-floating in the medium. One reason that carriers can float in the medium may be due to entrapped air on the textured surface of the carriers. For example, the carriers with concave textured surface may entrap air and therefore are prone to carrier floating. The floating carriers have limited exposure to cells and culture media, which affects cell seeding and thereby cell culture and growth.
Therefore, the carriers or a method of making such carriers which has enhanced wettability without permanently altering the surface chemistry or changing the environment of cell growth is highly desirable. The development of cell carriers that increase wettability to facilitate adherent cell attachment, proliferation and release, maintaining the quality and desired characterization of the cells under reduced shear forces is a long felt need.